Two kinesins drive anterograde neuropeptide transport

Lim, Angeline; Rechtsteiner, Andreas; Saxton, William M.

doi:10.1091/mbc.e16-12-0820

Cited by 41 publications

(51 citation statements)

References 65 publications

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“…While this kinesin could be kinesin-1 itself, it is also possible that an additional kinesin is involved in transporting outposts. The best candidates for such another kinesin would be kinesin-2 or kinesin-3, which co-transport some cargo with kinesin-1 (Guardia et al, 2016;Gumy et al, 2017;Hendricks et al, 2010;Kulkarni et al, 2017;Lim et al, 2017;Ruane et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts

Kelliher

Yue

et al. 2018

Preprint

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SummaryNeuronal polarity relies on the axon-or dendrite-specific localization of cargo by molecular motors such as kinesin-1. These studies show autoinhibition regulates both kinesin-1 activity and localization to keep dendritic cargo from entering axons. was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/275149 doi: bioRxiv preprint first posted online 1 AbstractNeuronal polarity relies on the selective localization of cargo to axons or dendrites. The molecular motor kinesin-1 moves cargo into axons but is also active in dendrites. This raises the question of how kinesin-1 activity is regulated to maintain the compartment-specific localization of cargo. Our in vivo structure-function analysis of endogenous Drosophila kinesin-1 reveals a novel role for autoinhibition in enabling the dendrite-specific localization of Golgi outposts.Mutations that disrupt kinesin-1 autoinhibition result in the axonal mislocalization of Golgi outposts. Autoinhibition also regulates kinesin-1 localization. Uninhibited kinesin-1 accumulates in axons and is depleted from dendrites, correlating with the change in outpost distribution and dendrite growth defects. Genetic interaction tests show that a balance of kinesin-1 inhibition and dynein activity is necessary to localize Golgi outposts to dendrites and keep them from entering axons. Our data indicate that kinesin-1 activity is precisely regulated by autoinhibition to achieve the selective localization of dendritic cargo.All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Section: Discussionmentioning

confidence: 99%

Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts

Kelliher

Yue

et al. 2018

Preprint

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“…The large number of kinesin genes raises a fundamental question: Why are so many motors required to fulfill what appears to be the same basic function of moving vesicles towards the plus‐end of microtubules? Some of the kinesin diversity may provide redundancy, but that alone is unlikely to explain the size of the kinesin family. Instead, the diversity could allow different kinesins to confer different transport parameters, targeting vesicles to specific destinations.…”

Section: Introductionmentioning

confidence: 99%

A novel strategy to visualize vesicle‐bound kinesins reveals the diversity of kinesin‐mediated transport

Yang

Bostick

Garbouchian

et al. 2019

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In mammals, 15 to 20 kinesins are thought to mediate vesicle transport. Little is known about the identity of vesicles moved by each kinesin or the functional significance of such diversity. To characterize the transport mediated by different kinesins, we developed a novel strategy to visualize vesicle‐bound kinesins in living cells. We applied this method to cultured neurons and systematically determined the localization and transport parameters of vesicles labeled by different members of the Kinesin‐1, ‐2, and ‐3 families. We observed vesicle labeling with nearly all kinesins. Only six kinesins bound vesicles that undergo long‐range transport in neurons. Of these, three had an axonal bias (KIF5B, KIF5C and KIF13B), two were unbiased (KIF1A and KIF1Bβ), and one transported only in dendrites (KIF13A). Overall, the trafficking of vesicle‐bound kinesins to axons or dendrites did not correspond to their motor domain preference, suggesting that on‐vesicle regulation is crucial for kinesin targeting. Surprisingly, several kinesins were associated with populations of somatodendritic vesicles that underwent little long‐range transport. This assay should be broadly applicable for investigating kinesin function in many cell types.

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“…With the original BirA ligase this technique has a documented labeling radius of ~10 nm (Kim et al, 2014) and is advantageous over classical coaffinity purification by allowing for detection of transient or weak molecular interactions. We found that a neuronally expressed fusion of the enhanced BirA variant TurboID (Branon et al, 2018) to gain-of-function Rab2 Q65L (TurboID-Rab2 Q65L ) biotinylates the main anterograde Drosophila DCV motor (Barkus et al, 2008;Lim et al, 2017), the Kinesin-3 unc-104 ( Fig. 6C).…”

Section: Rab2 Exhibits Activity-dependent Nanometer-range Proximity Tmentioning

confidence: 96%

“…Anterograde transport is mediated by the diverse family of plus-enddirected kinesin motors, while retrograde transport depends on cytoplasmic dynein. However, a high degree of interdependence exists between anterograde and retrograde transport (Barkus et al, 2008;Lim et al, 2017;Martin et al, 1999;Twelvetrees et al, 2016). Motor recruitment and regulation is mediated by adaptor proteins and small GTPases and is organelle-specific, producing different movement patterns for different organelles (Guedes-Dias and Holzbaur, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Motor recruitment and regulation is mediated by adaptor proteins and small GTPases and is organelle-specific, producing different movement patterns for different organelles (Guedes-Dias and Holzbaur, 2019). In both mammals and invertebrates, axonal transport of DCVs is mediated by the Kinesin-3 KIF1A/unc-104 and Kinesin-1 (Barkus et al, 2008;Gumy et al, 2017;Lim et al, 2017;Lo et al, 2011), but how these motors are recruited and regulated is not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Lund

Lycas

Schack

et al. 2020

Preprint

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Long range fast axonal transport of neuropeptide-containing dense core vesicles (DCVs), endolysosomal organelles and presynaptic components is critical for maintaining the functionality of neurons. How the transport of DCVs is orchestrated remains an important unresolved question.The small GTPase Rab2 has previously been shown to mediate DCV biogenesis and endosomelysosome fusion. Here we use the Drosophila model system to demonstrate that Rab2 also plays a critical role in bidirectional axonal transport of DCVs, endosomes and lysosomal organelles, most likely by controlling molecular motors. We further show that the lysosomal motility factor Arl8 is required as well for axonal transport of DCVs, but unlike Rab2 is also critical for DCV exit from cell bodies into axons. Our results uncover the mechanisms responsible for axonal transport of DCVs and reveal surprising parallels between the regulation of DCVs and lysosomal motility.

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Two kinesins drive anterograde neuropeptide transport

Abstract: Current anterograde transport models focus on one type of plus-end–directed kinesin for each type of cargo. This study shows that two anterograde motors, kinesin-1 and kinesin-3, both contribute to the transport of neuropeptide-filled vesicles in axons in vivo.

Cited by 41 publications

References 65 publications

Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts

Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts

A novel strategy to visualize vesicle‐bound kinesins reveals the diversity of kinesin‐mediated transport

Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

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